Usage
- Cilnidipine + Irbesartan is primarily indicated for the management of essential hypertension (high blood pressure) in adults.
- Pharmacological Classification: Antihypertensive (a combination of a calcium channel blocker and an angiotensin II receptor blocker).
- Mechanism of Action: Cilnidipine blocks L/N-type calcium channels, inhibiting calcium influx into vascular smooth muscle cells, leading to vasodilation. Irbesartan blocks angiotensin II receptors (AT1 subtype), preventing vasoconstriction and reducing blood pressure. The combined action results in synergistic blood pressure lowering.
Alternate Names
- Cilni-Irbe
- Granry-CL
- Dacia CL
- Clindasartan
- Various other brand names exist depending on the region and manufacturer.
How It Works
- Pharmacodynamics: Cilnidipine primarily affects peripheral arteries, causing vasodilation and reducing peripheral resistance. Irbesartan blocks the effects of angiotensin II, leading to vasodilation, reduced aldosterone secretion, and decreased sodium and water retention.
- Pharmacokinetics: Both drugs are orally administered. Cilnidipine is well-absorbed and extensively metabolized by the liver (CYP3A4). Irbesartan is also well-absorbed and partially metabolized by the liver (CYP2C9). Both drugs are primarily excreted via the biliary route (feces), with some renal excretion.
- Mode of Action: Cilnidipine inhibits calcium influx into vascular smooth muscle by binding to L/N-type calcium channels. Irbesartan competitively inhibits angiotensin II binding to AT1 receptors.
- Receptor Binding/Enzyme Inhibition: Cilnidipine binds to L/N-type calcium channels. Irbesartan competitively binds to AT1 receptors.
- Elimination Pathways: Primarily biliary/fecal excretion for both drugs, with some renal excretion. Cilnidipine is metabolized by CYP3A4 and Irbesartan by CYP2C9.
Dosage
Standard Dosage
Adults:
- Initial dose: Cilnidipine 5 mg + Irbesartan 150 mg once daily.
- Titration: May be increased to Cilnidipine 10 mg + Irbesartan 300 mg once daily as needed to control blood pressure.
Children:
- Safety and efficacy have not been established in children.
Special Cases:
- Elderly Patients: Consider a lower starting dose of Irbesartan (75 mg), particularly in patients over 75 years.
- Patients with Renal Impairment: Use with caution, especially if volume depleted. Dose adjustment may be required in severe renal dysfunction.
- Patients with Hepatic Dysfunction: Use with caution; dose adjustment may be needed.
- Patients with Comorbid Conditions: Careful monitoring is recommended, particularly in patients with heart failure, severe aortic stenosis, or other cardiovascular diseases.
Clinical Use Cases
- Cilnidipine + Irbesartan is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. It’s intended for chronic hypertension management.
Dosage Adjustments
- Dose modifications may be necessary based on patient response, renal or hepatic function, and concomitant medications.
Side Effects
Common Side Effects:
- Dizziness
- Headache
- Peripheral edema
- Fatigue
- Flushing
- Palpitations
- Nausea
Rare but Serious Side Effects:
- Angioedema
- Hypotension
- Hyperkalemia
- Renal failure
- Hepatotoxicity
Long-Term Effects:
- Potential long-term effects include cardiovascular events if hypertension remains uncontrolled.
Adverse Drug Reactions (ADR):
- Angioedema requires immediate medical attention.
Contraindications
- Hypersensitivity to Cilnidipine or Irbesartan.
- Pregnancy (especially second and third trimesters).
- Bilateral renal artery stenosis.
- Anuria.
Drug Interactions
- Other antihypertensives: May potentiate hypotensive effects.
- Potassium-sparing diuretics: Increased risk of hyperkalemia.
- Lithium: Increased lithium levels.
- CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, grapefruit juice): Increased cilnidipine levels.
- CYP2C9 inhibitors (e.g., fluconazole): May increase irbesartan levels.
Pregnancy and Breastfeeding
- Pregnancy: Contraindicated, especially in the second and third trimesters, due to the risk of fetal renal and pulmonary toxicity.
- Breastfeeding: Irbesartan may be excreted in breast milk. Use with caution and monitor the infant for potential side effects.
Drug Profile Summary
- Mechanism of Action: Cilnidipine: Calcium channel blocker (L/N-type); Irbesartan: Angiotensin II receptor blocker (AT1).
- Side Effects: Dizziness, headache, peripheral edema, fatigue, flushing, palpitations, nausea (common); angioedema, hypotension, hyperkalemia, renal failure, hepatotoxicity (rare but serious).
- Contraindications: Hypersensitivity, pregnancy, bilateral renal artery stenosis, anuria.
- Drug Interactions: Other antihypertensives, potassium-sparing diuretics, lithium, CYP3A4 and CYP2C9 inhibitors.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; use with caution during breastfeeding.
- Dosage: Adults: Cilnidipine 5-10 mg + Irbesartan 150-300 mg once daily. Adjustments may be necessary.
- Monitoring Parameters: Blood pressure, heart rate, renal function, electrolyte levels (potassium).
Popular Combinations
- May be combined with a thiazide diuretic (like hydrochlorothiazide or chlorthalidone) in cases of resistant hypertension.
Precautions
- Assess renal and hepatic function before initiating therapy.
- Monitor blood pressure and heart rate regularly.
- Caution in patients with severe aortic stenosis or heart failure.
- Avoid abrupt withdrawal.
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Use with caution and monitor infant.
- Children & Elderly: Not established in children; lower initial dose in elderly.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cilnidipine + Irbesartan?
A: Initial: Cilnidipine 5 mg + Irbesartan 150 mg once daily. May increase to 10 mg + 300 mg, respectively.
Q2: What are the common side effects?
A: Dizziness, headache, peripheral edema, fatigue, flushing, palpitations, and nausea.
Q3: Is Cilnidipine + Irbesartan safe in pregnancy?
A: No, contraindicated, especially during the second and third trimesters.
Q4: How does Cilnidipine + Irbesartan work?
A: Cilnidipine blocks calcium channels, causing vasodilation. Irbesartan blocks angiotensin II receptors, preventing vasoconstriction. The combination provides synergistic blood pressure lowering.
Q5: What are the potential drug interactions?
A: Interactions can occur with other antihypertensives, potassium-sparing diuretics, lithium, and CYP3A4/CYP2C9 inhibitors (e.g., ketoconazole, fluconazole, grapefruit juice).
Q6: How should I monitor a patient on this medication?
A: Monitor blood pressure, heart rate, renal function (serum creatinine), and electrolyte levels (potassium).
Q7: Are there any contraindications to using Cilnidipine + Irbesartan?
A: Hypersensitivity, pregnancy, bilateral renal artery stenosis, and anuria.
Q8: Can I use this medication in patients with renal impairment?
A: Use with caution, especially if they are volume depleted. Dose adjustment may be needed.
Q9: Can I use this medication in elderly patients?
A: Yes, but start with a lower dose of Irbesartan (75 mg), especially for patients over 75. Close monitoring is essential.
Q10: What should I do if a patient experiences angioedema while taking Cilnidipine + Irbesartan?
A: Discontinue the medication immediately and provide appropriate medical care. Angioedema is a serious side effect that requires prompt intervention.
